Type 2 Diabetes
Conditions
Keywords
Type 2 Diabetes
Brief summary
This study will test the hypothesis that the Final Market Image (FMI) sitagliptin/metformin 50 mg/500 mg and 50 mg/850 mg (Fixed Dose Combination) FDC tablet and co-administration of corresponding doses of sitagliptin and China-sourced metformin as individual tablets will be bioequivalent based on assessment of the AUC(0-t) and Cmax, for both sitagliptin and metformin.
Interventions
DRUGCo-administration of 50 mg sitagliptin and 500 mg metformin
Co-administration of 50 mg sitagliptin and 500 mg China-sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met500) after fasting for at least 10 hours.
DRUGsitagliptin/metformin 50 mg/500 mg tablet
Single dose administration of the final marketing image (FMI) sitagliptin/metformin 50 mg/500 mg fixed-dose combination (FDC) tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.
DRUGCo-administration of 50 mg sitagliptin and 850 mg metformin
Co-administration of 50 mg sitagliptin and 850 mg China sourced metformin as individual tablets with 240 ml water on Day 1 of the relevant treatment period (Sit + Met850) after fasting for at least 10 hours.
DRUGsitagliptin/metformin 50 mg/850 mg tablet
Single dose administration of the FMI sitagliptin/metformin 50 mg/850 mg FDC tablet with 240 ml water on Day 1 of the relevant treatment period (SitMet850 FDC) after fasting for at least 10 hours.
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
18 Years to 40 Years
Healthy volunteers
Yes
Inclusion criteria
* Subject is of Chinese descent * Subject is in good health * Subject is a non-smoker
Exclusion criteria
* Subject has a history of stroke or chronic seizures * Subject has a history of cancer * Subject has had major surgery, donated blood or participated in another investigational study within the past 4 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Area Under the Curve (AUC(0-t)) for Sitagliptin | baseline through 72 hours postdose | AUC (0-t) is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg. |
| Cmax for Sitagliptin and Metformin | baseline through 72 hours postdose | Cmax is the peak serum concentration of a therapeutic drug after administration; and is used to determine the rate and extent of drug absorption. Cmax is reported for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg. |
Participant flow
Recruitment details
28 participants were randomized in four treatment sequences. Participants had a 7 day minimum washout period between treatments.
Participants by arm
| Arm | Count |
|---|---|
| All Participants | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 28.6 years STANDARD_DEVIATION 5.61 |
| Body Mass Index (BMI) | 22 kg/m^2 STANDARD_DEVIATION 1.22 |
| Region of Enrollment China | 28 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 4 / 28 | 3 / 28 | 4 / 28 | 2 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 | 0 / 28 | 0 / 28 |
Outcome results
Primary
Area Under the Curve (AUC(0-t)) for Sitagliptin
AUC (0-t) is the area under the curve for the plot showing plasma concentration against time from time zero to the time of the last quantifiable concentration for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg.
Time frame: baseline through 72 hours postdose
Population: Per-Protocol (PP) set: Participants who completed the study according to the protocol. One participant who discontinued after Treatment Period 1 was not included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sit 50 mg + Met 500 mg | Area Under the Curve (AUC(0-t)) for Sitagliptin | sitagliptin 50 mg | 1570 hr*ng/mL | Standard Deviation 217.4 |
| Sit 50 mg + Met 500 mg | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 850 mg | NA hr*ng/mL | — |
| Sit 50 mg + Met 500 mg | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 500 mg | 8350 hr*ng/mL | Standard Deviation 1881.7 |
| SitMet 50mg/500mg FDC | Area Under the Curve (AUC(0-t)) for Sitagliptin | sitagliptin 50 mg | 1590 hr*ng/mL | Standard Deviation 186.58 |
| SitMet 50mg/500mg FDC | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 850 mg | NA hr*ng/mL | — |
| SitMet 50mg/500mg FDC | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 500 mg | 8750 hr*ng/mL | Standard Deviation 1920.45 |
| Sit 50 mg + Met 850 mg | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 500 mg | NA hr*ng/mL | — |
| Sit 50 mg + Met 850 mg | Area Under the Curve (AUC(0-t)) for Sitagliptin | sitagliptin 50 mg | 1520 hr*ng/mL | Standard Deviation 228.83 |
| Sit 50 mg + Met 850 mg | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 850 mg | 11800 hr*ng/mL | Standard Deviation 2849.36 |
| SitMet 50mg/850mg FDC | Area Under the Curve (AUC(0-t)) for Sitagliptin | sitagliptin 50 mg | 1600 hr*ng/mL | Standard Deviation 195.05 |
| SitMet 50mg/850mg FDC | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 850 mg | 13100 hr*ng/mL | Standard Deviation 2987.28 |
| SitMet 50mg/850mg FDC | Area Under the Curve (AUC(0-t)) for Sitagliptin | metformin 500 mg | NA hr*ng/mL | — |
Primary
Cmax for Sitagliptin and Metformin
Cmax is the peak serum concentration of a therapeutic drug after administration; and is used to determine the rate and extent of drug absorption. Cmax is reported for sitagliptin 50 mg, metformin 500 mg and metformin 850 mg.
Time frame: baseline through 72 hours postdose
Population: Per-Protocol (PP) set: Participants who completed the study according to the protocol. One participant who discontinued after Treatment Period 1 was not included in the analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sit 50 mg + Met 500 mg | Cmax for Sitagliptin and Metformin | sitagliptin 50 mg | 189 ng/mL | Standard Deviation 37.76 |
| Sit 50 mg + Met 500 mg | Cmax for Sitagliptin and Metformin | Metformin 850 mg | NA ng/mL | — |
| Sit 50 mg + Met 500 mg | Cmax for Sitagliptin and Metformin | Metformin 500 mg | 1210 ng/mL | Standard Deviation 323.83 |
| SitMet 50mg/500mg FDC | Cmax for Sitagliptin and Metformin | sitagliptin 50 mg | 182 ng/mL | Standard Deviation 38.71 |
| SitMet 50mg/500mg FDC | Cmax for Sitagliptin and Metformin | Metformin 850 mg | NA ng/mL | — |
| SitMet 50mg/500mg FDC | Cmax for Sitagliptin and Metformin | Metformin 500 mg | 1310 ng/mL | Standard Deviation 383.57 |
| Sit 50 mg + Met 850 mg | Cmax for Sitagliptin and Metformin | Metformin 500 mg | NA ng/mL | — |
| Sit 50 mg + Met 850 mg | Cmax for Sitagliptin and Metformin | sitagliptin 50 mg | 187 ng/mL | Standard Deviation 40.31 |
| Sit 50 mg + Met 850 mg | Cmax for Sitagliptin and Metformin | Metformin 850 mg | 1790 ng/mL | Standard Deviation 488.51 |
| SitMet 50mg/850mg FDC | Cmax for Sitagliptin and Metformin | sitagliptin 50 mg | 194 ng/mL | Standard Deviation 32.67 |
| SitMet 50mg/850mg FDC | Cmax for Sitagliptin and Metformin | Metformin 850 mg | 1970 ng/mL | Standard Deviation 482.69 |
| SitMet 50mg/850mg FDC | Cmax for Sitagliptin and Metformin | Metformin 500 mg | NA ng/mL | — |